e are investigating the regulation of expression of genes in he rabbit kappa (k) immunoglobulin (Ig) locus. Domestic abbits harbor Ig k sequences that give rise to two intense ands when genomic Southern blots are probed with a fragment of he cloned k1b4 gene. We have now cloned a k2b4 gene and a 1b5 gene; accumlulated evidence derived from all three genes dentifies the two intensely hybridizing Southern blot bands as ominal expressed k isotype gene and a k2 isotype gene. The k2 ene is apparently not expressed in domestic rabbits, although here are no obvious defects in the coding sequences of the loned k2b4 gene. The possibility that differential k1 vs k2 xpression results from different regulatory sequences in the k-Ck intron is currently being explored by inserting these ntro sequences into expression vectors to test their effects s enhancers of k gene transcription. In an attempt to nderstand latent k allotype expression in rabbits, we examined outhern blots of DNA from a rabbit in our colony that xpressed latent allotype; no "extra" Southern blot bands that ight have encoded latent allotype were observed. ur studies of gene activation in human B cell development have hifted emphasis from the attempts to advance developmental tages of B cell lines in vitro to studies of the chromosomal tate of regulatory regions, especially in the human k gene. e plan to apply the high-resolution Southern blot technology eveloped for genomic DNA sequencing to examine DNAase ypersensitivity sites in the human k enhance and to look for ifferences between k-expressing and non-expressing cell lines ith respect to DMS protection (footprinting) and Exonuclease II susceptibility in this region.